ZYRTEC Tablet

Cetirizine is contraindicated in :

・hypersensitivity to any of constituents of this formulation, to hydroxyzine or to any piperazine derivatives,

・patients with severe renal impairment at less than 10 ml/min creatinine clearance.

Due to the pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400mg/body).

Fertility

There are no relevant data available.

Pregnancy

Caution should be exercised when prescribing to pregnant women.

For cetirizine very rare clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Lactation

Caution should be exercised when prescribing cetirizine to lactating women. Cetirizine is excreted in human milk at concentrations representing 25% to 90% of those measured in plasma, depending on sampling time after administration.

Alcohol

At therapeutic doses, no clinically significant interactions have been demonstrated with alcohol (for a blood alcohol level of 0.5g/L). Nevertheless, precaution is recommended if alcohol is taken concomitantly.

Increased risk of urinary retention

Caution should be taken in patients with predisposition factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as cetirizine may increase the risk of urinary retention.

Patients at risk of convulsions

Caution in epileptic patients and patients at risk of convulsions is recommended.

Children

The use of the film-coated tablet formulation is not recommended in children aged less than 6 years since this formulation does not allow for appropriate dose adaptation. It is recommended to use a paediatric formulation of cetirizine.

The half-life of cetirizine was about 6 hours in children of 6-12 years and 5 hours in children 2-6 years.

Elderly, Renal/Hepatic impairment

See package insert.

Allergy skin tests

Allergy skin tests are inhibited by antihistamines and a wash-out period of 3 days is recommended before performing them.

Food

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

Excipients

Lactose

Film-coated tablet, 10mg

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, (the Lapp lactase deficiency or glucose-galactose malabsorption) should not take this medicine.

Sorbitol

Oral solution, 1mg/ml

This product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Sucrose

Oral solution, 1mg/ml

This product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucosegalactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Parabens

Oral solution, 1mg/ml

This product contains methylparahydroxybenzoate or propylparahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Cetirizine, a human metabolite of hydroxyzine, is a potent and selective antagonist of peripheral H1-recptors. In vitro receptor binding studies have shown no measurable affinity for receptors other than H1-receptors.

Ex vivo experiments in mice have shown that systemically administered cetirizine does not significantly occupy the cerebral H1-receptors.

In addition to its anti-H1 effect, cetirizine was shown to display anti-allergic activities: at a dose of 10mg once or twice daily, it inhibits the late phase recruitment of inflammatory cells, notably eosinophils, in the skin and conjunctiva of atopic subjects submitted to antigen challenge, and the dose of 30mg/day inhibits the influx of eosinophils in the bronchoalveolar lavage fluid during a late-phase bronchial constriction induced by allergen inhalation in asthmatic subjects. Moreover, cetirizine inhibits the late-phase inflammatory reaction induced in chronic urticaria patients by intradermal administration of kallikrein. It also down-regulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, which are markers of allergic inflammation.

Studies in healthy volunteers show that cetirizine, at doses of 5 and 10mg strongly inhibits the wheal and flare reactions induced by very high concentrations of histamine into the skin. The onset of activity after a single 10mg dose occurs within 20 minutes in 50% of the subjects and within one hour in 95%. This activity persists for at least 24 hours after a single administration. In a 35-day study in children aged 5-12, no tolerance to the antihistaminic effect (suppression of wheal and flare) of cetirizine was found. When a treatment with cetirizine is stopped after repeated administration, the skin recovers its normal reactivity to histamine within 3 days.